Prof Dr Johnson Stanslas on approaches of pharmacotherapeutic research and his insistence on strong fundamental research

BY: SYAMIL ZAHARI

B

efore clinicians prescribe therapeutic drugs to patients, there is plenty of work to be done in order to turn pre-clinical and development research into approved health products with real-world benefits.

ai???This is where our role comes in: the discovery part and translational research,ai??? shared Prof Dr Johnson Stanslas, head of Pharmacotherapeutics Unit in the Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia.

ai???Whatever findings we get in the lab have to be translated to patients. And that means thereai??i??s a lot of steps we have to take,ai??? he said during an exclusive interview with AMOR Media.

ai???For example, in a drug discovery, the first stage is where you start with non-human models. That means you work with cells, you work with animals and very often these models are not perfect because they are models. So you have to make sure that whatever outcome that you get from these models, they could be translated in such a way that you can get meaningful result in the humans.ai???

Stanslasai??i?? research also extends to efficacy and toxicity studies of cytotoxic and molecular targeted agents in cancer patients with the aim of translating the laboratory findings to the clinic for improvement of cancer management.

ai???Part of my research is to investigate chemotherapy drugs effects in patients. The major problems with this kind of cancer drugs are mainly toxicity and low efficacy ai??i?? how to improve drugs when some patients are having toxicity whereas others donai??i??t show any efficacy.ai???

Fundamental science

However, according to Stanslas, among key challenges in the field of drug discovery is the pressure of being expected to come up with a product within a very short timeframe.

Researchers in Malaysia, rued Stanslas, however are often not given sufficient time and funding. ai???[The research sponsors in Malaysia] expect you to come up with some products very fast. Even when you apply for grants, or consideration of the existing grant, they will ask you what the discovery is from the previous grant.ai???

In addition, if the research is more geared towards fundamental, the sponsors would question the studyai??i??s profitability. ai???What they donai??i??t realise is that all research that is subtle or with fundamental approach will ultimately come up with some product, but itai??i??s not immediate,ai??? he asserted.

ai???We are basically impatient,ai??? Stanslas said of the Malaysian research environment. ai???We are progressing very slowly, but the approach has to be changed,ai??? he added.

Part of the transformation needed in the approach in cancer drug discovery has to do with the mindset of local researchers. Typically, according to Stanslas, researchers in advanced nations will focus their attention on the target they are trying to destroy. ai???Researchers would start with doing a lot of computational studies. Then theyai??i??d design the drug, and only after that would they put the drug to test,ai??? Stanslas explained.

In developed countries, researchers always start with fundamental science first, according to Stanslas. ai???They know the pathway they want to eradicate, so they would design drugs against this pathway,ai??? he said. ai???But we [Malaysian researchers] do it in a sort of a different way. We screen a lot of test agents, which is still relevant, but we donai??i??t know exactly how it will work. We test for activities without knowing what pathway these molecules act on, and hope we will find the pathway.ai???

ai???I believe that you need to put in good science ai??i?? strong science ai??i?? into every discovery.ai??? ai??i?? Prof Dr Stanslas

Blockbuster drug

Stanlas reiterated the importance of fundamental science and of granting enough time and funding for cancer researchers. He related the story of (now Emeritus) Prof Malcolm Stevens, his doctoral research supervisor while at the University of Nottingham, United Kingdom. ai???[Stevens] took almost 30 years ai??i?? almost all his professional life ai??i?? to bring a drug to patients. He discovered it when he was doing his PhD,ai??? Stanslas recalled. ai???Itai??i??s now in the market, a drug called Temozolomide.ai???

Stevens led a team of Aston University researchers in late 1970s, with steadfast funding from Cancer Research UK without pressing commercial or legal interests, before his teamai??i??s laborious testing finally discovered molecules in 1987 that would eventually became Temozolomide, and yet another decade would pass before the drug was approved for worldwide release in year 2000.

ai???One drug, and thatai??i??s [Stevenai??i??s] whole life ai??i?? and heai??i??s only now enjoying the sacrifices he has made,ai??? Stanslas said.

The oral chemotherapy drug Temozolomide is so successful that it is now the international modern standard-of-care for thousands of patients being treated for glioblastoma, the most common adult brain tumour.

The blockbuster drug also now has global sales of over USD1bil annually, with its royalty money being pumped back into Cancer Research UKai??i??s studies to fund more new studies on the prevention, diagnosis and treatment of cancer.

The story of Temozolomide has been widely commended as a textbook example of effective multidisciplinary collaboration by researchers from various fields (crystallography, pharmacology, pharmaceutics, molecular biology, pharmacogenetics, etc.) with strong support from governmental organizations and private interests to develop a valuable health product.

ai???I believe that you need to put in good science ai??i?? strong science ai??i?? into every discovery,ai??? Stanslas said. ai???It takes time to come up with a product. If your drug has been meticulously tested or assessed for all possible effects, not only just the efficacy but also side effects, then nobody is going to challenge that itai??i??s going to have a big problem.ai???

He re-emphasized: ai???This means time is a factor, money is a factor, policy is a factor.ai???

Stanslas is now actively involved in the discovery and preclinical development of new anticancer and anti-inflammatory agents (for neurological and pulmonary disorders) and to date he has been successful in discovering lead anticancer molecules for the treatment of breast, prostate and colon cancers. In addition, translational medicine research (e.g. pharmacogenomics study) remains as an integral part of his research group.

Stanslasai??i?? current translational research in neuroscience, particularly in personalizing drugs for stroke, is currently being pursued via the Neuroscience Cluster of Faculty of Medicine and Health Sciences, Universiti Putra Malaysia.